1. Field of the Invention
The present invention relates to grhelin O-acyltransferase inhibitors and, more specifically, a small molecule peptidomimetic inhibitor targeting ghrelin O-acyltransferase.
2. Description of the Related Art
Ghrelin is a peptide hormone involved in appetite stimulation, regulation of glucose homeostasis, and a range of other physiological processes. Ghrelin requires a unique posttranslational modification, octanoylation of a serine side chain, to bind its cognate receptor and activate signaling. The enzyme that catalyzes this modification, ghrelin O-acyltransferase (GOAT), is receiving increased interest as a potential drug target for treatment of obesity, diabetes, and other diseases potentially linked to ghrelin signaling. As ghrelin is the only known substrate of GOAT, blocking ghrelin acylation using GOAT inhibitors potentially offers a specific and targeted avenue to treat diabetes, obesity, and other health conditions impacted by ghrelin signaling. Generating hGOAT inhibitors presents a significant challenge, however, due to the complete lack of structural information and minimal mechanistic information available regarding hGOAT. As a result, very little rational drug design can be carried out.